Rejection is the major cause of failure of human kidney transplants. Humoral antibody is probably responsible for the majority of these rejections because current immunosuppressive regimens are much more successful in preventing and reversing cellular rejection. Progress has been handicapped by the lack of a method which was sensitive enough to detect humoral antibodies in the circulation of a patient with a functioning kidney transplant. In these studies, a modification of the mixed antiglobulin reaction will be employed to study the development of donor specific IgG antibody in renal transplant recipients. This method has been demonstrated to be sensitive enough to detect IgG antibody directed against donor kidney cells in the transplant and correlates in preliminary studies with chronic rejection. The development of antibody will be correlated with the type of rejection, the HL-A match of the transplant, recipient splenectomy, blood transfusions, pathology of the transplants and other factors as well as transplant and recipient survival. The specificity of antibodies developing in response to a transplant will be studied to determine whether or not they are directed solely against HL-A antigens or against other histocompatibility antigens (LD locus) as well. The reactivity of peripheral blood lymphocytes and kidney cells with antibodies from allograft recipients will be compared. The influence of enzymes, tissue culture and storage by freezing on the surface antigens of kidney cells will also be studied. Finally, the usefulness of a prospective kidney cell crossmatch by the mixed antiglobulin technique will be evaluated in the selection of recipients for cadaver kidney transplantation.